CAREER: Museomic approach for exploring the evolution of past, persistent, and emerging orthopoxvirus outbreaks

确定病毒可以感染哪些动物，仍然是了解病原体如何在自然种群中维持及其对人类的潜在溢出威胁的主要障碍。天花是人类历史上最致命的病原体之一，对于包括天花在内的一组病毒来说尤其如此。与这种致命大流行有关的一个主要未解问题是，为什么有些种类的痘病毒能够感染多种动物，而另一些只能感染一种动物。猴痘是一种能够感染多个物种的痘病毒，鉴于最近暴发的猴痘疫情，特别重要的是需要更好地了解宿主痘病毒的多样性和进化。该项目将使用新技术，结合保存在自然历史博物馆的历史和现代动物样本，扩大我们对生命之树中痘病毒感染的理解。此外，该项目通过增加STEM的多样性，并通过将未被充分代表的少数民族置于前沿研究的中心，创造多元化的劳动力队伍，从而推进了NSF的目标。具体来说，这项工作涉及到将一个主要为本科生和少数族裔服务的机构与芝加哥及其他地区的几家一流研究机构的合作伙伴联系起来，为参与该项目的学生创造一个机会网络。该项目将利用来自已知发生痘疫情的地区和时期的大量历史博物馆标本，并推进基因组技术，以扩大我们对痘病毒进化和宿主多样性的了解。拟议的工作将集中在三个博物馆藏品上，目标是：过去的一次爆发（天花）；目前的疫情（猴痘）；最后是一种新出现的威胁（阿拉斯加痘）。利用高通量测序和靶向富集方法的结合，将从痘阳性样本中生成病毒基因组，使研究人员能够阐明这些复杂但研究较少的病原体的进化史。这些数据将用于回答一系列与正痘病毒进化相关的问题，包括：1)基因组结构如何影响不同种类痘病毒的宿主范围？2)中间宿主或远亲宿主是否在正痘病毒多样化或传播中起作用？3)增加哺乳动物中正痘病毒的已知多样性是否有助于解决人类天花的系统发育位置和起源？该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Determining which animals a virus can infect remains a major obstacle for understanding how pathogens are maintained in natural populations and their potential spillover threat to humans. This is especially true for the group of viruses that includes smallpox, one of the deadliest pathogens in human history. A major unanswered question tied to this deadly pandemic is why some species of pox viruses are able to infect multiple animals while others only infect one. In light of the recent outbreak of monkeypox, a pox virus capable of infecting multiple species, the need to better understand host-pox virus diversity and evolution is of particular importance. This project will use novel technologies combined with historic and modern samples of animals housed in natural history museums to expand our understanding of pox virus infection across the tree of life. Additionally, this project advances the goals of the NSF by increasing diversity in STEM and creating a diverse workforce by placing underrepresented minorities at the center of cutting-edge research. Specifically, this work involves linking a primarily undergraduate, minority-serving institution with partnerships at several premier research institutions in Chicago and beyond, creating a network of opportunities for students engaged in the project. This project will leverage a large series of historical museum specimens from regions and time periods when pox outbreaks were known to occur, and advance genomic techniques to expand our knowledge of pox-virus evolution and host diversity. The proposed work will focus on three museum collections, targeting: a past outbreak (smallpox); a current outbreak (monkeypox); and finally, an emerging threat (Alaskapox). Viral genomes will be generated from pox-positive samples using a combination of high throughput sequencing and targeted enrichment approaches, allowing researchers to elucidate the evolutionary history of these complex but little-studied pathogens. Such data will be used to answer a suite of questions related to the evolution of Orthopoxvirus including: 1) How does genome architecture influence host range for different species of pox viruses? 2) Do intermediate hosts or distantly related hosts play a role in Orthopoxvirus diversification or transmission? and 3) Does increasing the known diversity of Orthopoxvirus in mammals help resolve the phylogenetic position and origin of human smallpox?This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.